9H81

human carbonic anhydrase I in complex with Sonepiprazole

This is a non-PDB format compatible entry.

Summary for 9H81

• Entry DOI: 10.2210/pdb9h81/pdb
• Descriptor: Carbonic anhydrase 1, ZINC ION, Sonepiprazole, ... (4 entities in total)
• Functional Keywords: carbonic anhydrase i, sulfonamide, inhibitor, metalloenzyme, sonepiprazole, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 58746.23

Authors

Angeli, A.,Ferraroni, M. (deposition date: 2024-10-28, release date: 2025-09-03)

Primary citation

Angeli, A.,Ferraroni, M.,Capasso, C.,Supuran, C.T.
Structural Studies of the Dopamine D 4 Receptor Antagonist Sonepiprazole as an Inhibitor of Human Carbonic Anhydrases.
Acs Med.Chem.Lett., 16:483-486, 2025

PubMed Abstract: In this study, we provide the first evidence that sonepiprazole, a dopamine D receptor antagonist, acts as a potent inhibitor of human carbonic anhydrases (hCAs). Sonepiprazole exhibited significant inhibitory activity across the panel of catalytically active hCAs, with the exception of hCA IV, and hCA III. The most potent inhibition was observed against the brain-associated isoform hCA VII, with a of 2.9 nM. Insights from X-ray crystallographic structures of the complexes with hCA I, hCA II, and hCA XII revealed that the sulfonamide group of sonepiprazole coordinates the zinc ion in the active site, a typical interaction for this class of inhibitors. Despite the presence of isoform-specific residues at the rim of the active site pocket, these variations seem not to significantly impact the compound overall inhibition potency. These findings highlight a dual functionality of sonepiprazole as both a D receptor antagonist and a carbonic anhydrase inhibitor.

PubMed: 40104783
DOI: 10.1021/acsmedchemlett.5c00034

Experimental method

X-RAY DIFFRACTION (2.35 Å)